Abstract:Attention-deficit/hyperactivity disorder (ADHD) symptoms are associated with an increased risk of smoking, and genetic studies have identified similar candidate genes associated with both ADHD and smoking phenotypes. This paper addresses the question of whether ADHD symptoms interact with candidate gene variation to predict smoking risk. Participants were a subsample of individuals from the National Longitudinal Study of Adolescent Health (Add Health), a nationally representative sample of adolescents followed from 1995 to 2002. The sample analyzed included a subset from Add Health of 1,900 unrelated individuals with genotype data. Multiple logistic regression was used to examine relationships between self-reported ADHD symptoms, genotype, and lifetime history of regular smoking. Polymorphisms in the DRD2 gene and, among females, the MAOA gene interacted with retrospective reports of ADHD symptoms in contributing to risk for smoking. Trends were observed for interactions between the DRD4 gene and, among males, the MAOA gene and ADHD symptoms to predict smoking risk. No main effect for any of these polymorphisms was observed. We observed neither main effects nor interactions with CYP2A6, DAT, and SLC6A4 genes. These findings suggest that genotypes associated with catecholamine neurotransmission interact with ADHD symptoms to contribute to smoking risk.